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Combining endocytosis and signalling...

Members of the low-density lipoprotein (LDL) receptor family have dual roles in endocytosis and signalling. Megalin, for example, mediates endocytic uptake of vitamin D metabolites in the kidney and also appears to act as a receptor for sonic hedgehog during forebrain development. Quite how such receptors combine their endocytic and signalling roles is unclear, but adaptor proteins containing PTB domains, PDZ domains or ankyrin repeats are thought to play a part. Thomas Willnow and co-workers have used a two-hybrid approach to identify a novel class of megalin adaptor: megalin-binding protein (MegBP). MegBP is a 350-residue protein that contains two tetratrico peptide repeats (motifs implicated in protein—protein interactions) and binds to a proline-rich region in the megalin cytoplasmic tail (see p. 453). The authors show that MegBP functionally interacts with megalin in vivo. Moreover, they find that it also binds to a variety of signalling molecules and transcriptional regulators. Interestingly, these include SKI-interacting protein (SKIP), a coactivator for the vitamin D receptor. An attractive hypothesis is therefore that MegBP acts by sequestering transcription factors involved in megalin signalling and releasing them after endocytic uptake of incoming ligands.

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Functional interaction of megalin with the megalinbinding protein (MegBP), a novel tetratrico peptide repeat-containing adaptor molecule

Helle Heibroch Petersen, Jan Hilpert, Daniel Militz, Valerie Zandler, Christian Jacobsen, Anton J. M. Roebroek, and Thomas E. Willnow
JCS 2003 116: 453-461. [Abstract] [Full Text]  

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JCS Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content Social Bookmarking                         What's this?